The so-called “successive seeded emulsion polymerization” technique, is a method of activated swelling of polymer particles. Importantly, the process allows the preparation of monodisperse spherical beads of predictable size from 1 to 100 μm in diameter (Ugelstad J. et al., Blood Purif. 11 (1993) 349-369). The polymer particles may be prepared from a number of different monomeric materials and with various morphologies including macroporous structures.
WO 2000/61647 discloses a process for the preparation of monodisperse polymer particles which are formed by contacting monomers with aqueous dispersions comprising monodisperse swellable seed polymers/oligomers, and initiating polymerisation in the presence of a steric stabilizer. The resulting swollen seed particles are characterised by the particle mode diameter.
The porous beads form the basis for magnetizable monodisperse polymer particles comprising magnetic iron oxides as small grains, e.g. present in the pore volumes of the beads. To this end, WO 2000/61647 mentions the concept coating of monodisperse polymer particles with magnetic coatings as a subsequent step after the swelling and polymerization steps. However, U.S. Pat. No. 4,707,523 particularly discloses preparation of monodisperse polystyrene microparticles. In an exemplary process, polystyrene seed particles were grown to a larger size by swelling the seed particles in a stirred emulsion comprising water, cyclohexane, styrene, divinyl benzene, benzoyl peroxide, and sodium dodecylsulfate. After a certain amount of time during which swelling was allowed to take place, the temperature of the mixture was raised, thereby starting the polymerization process which took place for a further amount of time. The resulting polystyrene microparticles were subsequently nitrated with concentrated H2SO4/HNO3, thereby functionalizing the polymer with —NO2 (nitro) groups. Such functionalized polymer particles were finally reacted with Fe powder in the presence of HCl, thereby oxidizing iron with the nitro groups. The reaction leads to a deposit of iron oxide on the surface of the polystyrene microparticles, as well as on the accessible surface of pores which may be present in the particles. Notably, the process of U.S. Pat. No. 4,707,523 is made up of three separate major steps—(i) generation of monodisperse particles, (ii) nitration of the particles, and (iii) metal oxide deposition. The nitration step requires the use of aggressive chemicals and therefore rather complex equipment for safe routine synthesis on a larger scale.
EP 1 391 899 A1 discloses another process for producing magnetic polymer particles. Firstly, there is provided a powder of hydrophobic polymer particles such as polystyrol particles which may be obtained as monodisperse polymer particles by way of a successive seeded emulsion polymerization process. The document discloses the first step of forming a colloidal dispersion, the dispersion comprising the particles as provided, further a finely divided magnetic material, e.g. in the form of a ferrofluid, and a non-polar organic solvent capable of penetrating the polymer particles. Thus, the ingredients were mixed to form a colloidal dispersion, incubation of which resulted in the swelling of the hydrophobic powder. During the swelling the polymer particles imbibed magnetic material. In a subsequent step, the non-polar organic solvent was removed, e.g. by way of evaporation or extraction, thereby resulting in polymer particles with trapped magnetic material. Notably, the EP 1 391 899 A1 discloses that the process may need to be performed repeatedly. Thus, the process might require further effort in order to achieve uptake of magnetic material in a desired quantity and/or with a desired reproducibility.
U.S. Pat. No. 4,339,337 discloses a process for the preparation of magnetic beads of vinylaromatic polymers, the process comprising the steps of dispersing a finely divided magnetic material in a solution of a polymerizeable vinylaromatic monomers, putting the resulting dispersion into suspension in water, and polymerizing the monomers. Exempary processes disclosed in the document show the production of magnetic particles having different sizes. The document appears to be silent regarding monodisperse particles.
U.S. Pat. No. 4,358,388 discloses a process for preparing magnetic-polymer latices. Magnetically charged particles are dispersed in an organic phase comprising an organically soluble initiator and an organic monomeric component such as a vinyl aromatic monomer. The dispersion is mixed with an aqueous solution containing an emulsifying agent and homogenized. Polymerization is then effected to form a magnetic polymer latex. In an embodiment, organic monomer component may be added immediately prior to or during polymerization.
The object of the disclosure reported herein was to establish a simple, fast and reproducible method to produce magnetic polymer particles which are monodisperse and contain a defined amount of magnetic material, wherein the magnetic material is evenly distributed throughout the entire volume of the polymer particle. Furthermore, it was an object to provide magnetic polymer particles which encase the magnetic material such that leaching is greatly reduced or substantially absent.